Exploration of Mutations of Alpha-1-Antitrypsin

  • Shelley Edwards
  • Robby Sanders


Alpha-1-Antitrypsin is a protein that functions as a protease inhibitor specifically for neutrophil elastase, an enzyme which breaks down elastin in the lungs. Mutations in the Alpha-1-Antitrypsin gene can ultimately result in various liver and lung diseases from deficient or ineffective protein. Literature searches were conducted to (1) gather information on normal and abnormal amino acids and corresponding codon sequences in the gene, (2) effects on the body, and (3) susceptibility of disease for the most prevalent mutations that cause a deficiency in Alpha-1-Antitrypsin. Having this resource of information divided into four categories (normal, deficient, null, and dysfunctional) will aid in creating a library of mutated forms of Alpha-1-Antitrypsin in the laboratory. Understanding and having access to the null mutant form, Hong Kong which results in a truncated form of Alpha-1 Antitrypsin, as well as other mutated versions will allow for future studies of inhibitory capacity of various forms of Alpha-1 Antitrypsin.  Studies to be conducted in the near future include: (1) using a restriction enzyme other than EcoRI in an effort to cut the Null-Hong Kong gene from a plasmid stored in the lab (a process that has not worked using EcoRI), (2) checking that the plasmid has the correct gene sequence that codes for the truncated form, and (3) exploring the viability of an alpha complementation experiment to confirm that the mutated form is inserted into the plasmid.